A retrospective study for the presence of lymphocytotoxic antibodies was performed on sera collected from 119 kidney graft recipients. Sera that had been collected on days 12 to 19 post-transplant were tested for cytotoxic reactions against a panel of human peripheral blood lymphocytes from 60 unrelated donors and 37 to 47 cultured human lymphoid cell lines (LCL). Forty-nine sera were negative against peripheral blood lymphocytes but contained cytotoxic antibody against cells on the LCL panel. Several sera were tested on E rosette-purified peripheral blood lymphocyte B cells and T cells from five donors whose LCL had also been tested. LCL appeared to be more sensitive to cytotoxic reactions than their B cell counterparts and may identify additional specificities which may not be related to the B cell alloantigenic system. Mixed lymphocyte culture blocking experiments were carried out against all combinations of these five cells. Some sera showed reactions of identity for B cells and LCL, and blocked the appropriate stimulator cells in mixed lymphocyte culture. Two sera that were positive for LCL but negative for B cell blocked only responder cells in the mixed lymphocyte culture.